A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy
| العنوان: | A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy |
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| المؤلفون: | Yuchen Li, Wanjing Feng, Xiao-Dong Zhu, Bingqiu Xiu, Shenglin Huang, Siyuan Chen, Qin Li, Yixiao Luo, Hongyan Lai, Ziteng Li, Yan Li |
| المصدر: | EBioMedicine EBioMedicine, Vol 62, Iss, Pp 103074-(2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, PCPG, pheochromocytoma and paraganglioma, Proteomics, Transcription, Genetic, Receptor, ErbB-2, medicine.medical_treatment, CHOL, cholangiocarcinoma, KIRP, kidney renal papillary cell carcinoma, lcsh:Medicine, KICH, kidney chromophobe, SKCM, skin cutaneous melanoma, HNSC, head and neck squamous cell carcinoma, THYM, thymoma, UVM, uveal melanoma, Targeted therapy, Machine Learning, 0302 clinical medicine, Neoplasms, Databases, Genetic, LIHC, liver hepatocellular carcinoma, TGCT, testicular germ cell tumors, BRCA, breast invasive carcinoma, OV, ovarian serous cystadenocarcinoma, Molecular Targeted Therapy, skin and connective tissue diseases, lcsh:R5-920, READ, rectum adenocarcinoma, PAAD, pancreatic adenocarcinoma, Disease Management, CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma, General Medicine, ACC, adrenocortical carcinoma, HER2-amplification, LUAD, lung adenocarcinoma, DLBC, lymphoid neoplasm diffuse large b-cell lymphoma, UCS, uterine carcinosarcoma, pCR, pathological complete response, RFS, recurrence-free survival, UCEC, uterine corpus endometrial carcinoma, 030220 oncology & carcinogenesis, SARC, sarcoma, Biomarker (medicine), Sarcoma, Disease Susceptibility, lcsh:Medicine (General), Research Paper, medicine.medical_specialty, MESO, mesothelioma, DNA Copy Number Variations, Clinical Decision-Making, Pan-cancer, STAD, stomach adenocarcinoma, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Multi-omics analysis, Breast cancer, Internal medicine, LGG, brain lower grade glioma, THCA, thyroid carcinoma, medicine, Biomarkers, Tumor, COAD, colon adenocarcinoma, Humans, LAML, acute myeloid leukemia, Lung cancer, neoplasms, ESCA, esophageal carcinoma, Bladder cancer, business.industry, Gene Expression Profiling, lcsh:R, Head and neck cancer, Gene Amplification, Computational Biology, LUSC, lung squamous cell carcinoma, Biomarker, GBM, glioblastoma multiforme, medicine.disease, Head and neck squamous-cell carcinoma, PRAD, prostate adenocarcinoma, 030104 developmental biology, Gene Expression Regulation, BLCA, bladder urothelial carcinoma, KIRC, kidney renal clear cell carcinoma, HER2-enriched subtype, business |
| الوصف: | Background The prevalence of HER2 alterations in pan-cancer indicates a broader range of application of HER2-targeted therapies; however, biomarkers for such therapies are still insufficient and limited to breast cancer and gastric cancer. Methods Using multi-omics data from The Cancer Genome Atlas (TCGA), the landscape of HER2 alterations was exhibited across 33 tumor types. A HER2 index was constructed using one-class logistic regression (OCLR). With the predictive value validated in GEO cohorts and pan-cancer cell lines, the index was then applied to evaluate the HER2-enriched expression pattern across TCGA pan-cancer types. Findings Increased HER2 somatic copy number alterations (SCNAs) could be divided into two patterns, focal- or arm-level. The expression-based HER2 index successfully distinguished the HER2-enriched subtype from the others and provided a stable and superior performance in predicting the response to HER2-targeted therapies both in breast tumor tissue and pan-cancer cell lines. With frequencies varying from 12.0% to 0.9%, tumors including head and neck squamous tumors, gastrointestinal tumors, bladder cancer, lung cancer and uterine tumors exhibited high HER2 indices together with HER2 amplification or overexpression, which may be more suitable for HER2-targeted therapies. The BLCA.3 and HNSC.Basal were the most distinguishable subtypes within bladder cancer and head and neck cancer respectively by HER2 index, implying their potential benefits from HER2-targeted therapies. Interpretation As a pan-cancer predictive biomarker of HER2-targeted therapies, the HER2 index could help identify potential candidates for such treatment in multiple tumor types by combining with HER2 multi-omics features. The discoveries of our study highlight the importance of incorporating transcriptional pattern into the assessment of HER2 status for better patient selection. Funding The National Key Research and Development Program of China; Clinical Research and Cultivation Project of Shanghai ShenKang Hospital Development Center. |
| اللغة: | English |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5788e8600642388a36fab4a55997452Test http://europepmc.org/articles/PMC7670125Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e5788e8600642388a36fab4a55997452 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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